Journal article
A novel HER2 gene body enhancer contributes to HER2 expression
Oncogene, Vol.37(5), pp.687-694
02/01/2018
DOI: 10.1038/onc.2017.382
PMCID: PMC5794618
PMID: 29035388
Abstract
The transcriptional regulation of the human epidermal growth factor receptor-2 (
HER2
) contributes to an enhanced
HER2
expression in HER2-positive breast cancers with
HER2
gene amplification and HER2-low or HER2-negative breast cancers following radiotherapy or endocrine therapy, and this drives tumorigenesis and the resistance to therapy. Epigenetic mechanisms are critical for transcription regulation, however, such mechanisms in the transcription regulation of
HER2
are limited to the involvement of tri-methylated histone 3 lysine 4 (H3K4me3) and acetylated histone 3 lysine 9 (H3K9ac) at the
HER2
promoter region. Here, we report the identification of a novel enhancer in the
HER2
3’ gene body, which we have termed
HER2
gene body enhancer (HGE). The HGE starts from the 3’ end of intron 19 and extends into intron 22, possesses enhancer histone modification marks in specific cells and enhances the transcriptional activity of the
HER2
promoters. We also found that TFAP2C, a known regulator of HER2, binds to HGE and is required for its enhancer function and that DNA methylation in the HGE region inhibits the histone modifications characterizing enhancer and is inversely correlated with
HER2
expression in breast cancer samples. The identification of this novel enhancer sheds a light on the roles of epigenetic mechanisms in
HER2
transcription, in both HER2-positive breast cancer samples and individuals with HER2-low or HER2-negative breast cancers undergoing radiotherapy or endocrine therapy.
Details
- Title: Subtitle
- A novel HER2 gene body enhancer contributes to HER2 expression
- Creators
- Q Liu - , Iowa City, IAM V Kulak - , Iowa City, IAN Borcherding - , Iowa City, IAP K Maina - , Iowa City, IAW Zhang - , Iowa City, IAR J Weigel - , Iowa City, IAH H Qi - , Iowa City, IA
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.37(5), pp.687-694
- DOI
- 10.1038/onc.2017.382
- PMID
- 29035388
- PMCID
- PMC5794618
- NLM abbreviation
- Oncogene
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 02/01/2018
- Academic Unit
- Dermatology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984024540102771
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